【摘要】 目的 探讨酸枣仁多糖(ZSSP)对慢性不可预测性温和应激(CUMS)抑郁症小鼠抑郁行为的影响及作用机制。方法 将60只SPF级昆明雄性小鼠随机均分为对照组、模型组、小剂量组、中剂量组、高剂量组和盐酸氟西汀(Flu)组，除对照组外，其余5组均采用CUMS法制备小鼠抑郁症模型，小剂量、中剂量和高剂量组分别采用50、100、150 mg/kg的ZSSP进行灌胃处理，对照组和模型组用0.9%氯化钠注射液灌胃，Flu组用10 mg/kg的Flu灌胃。比较各组小鼠抑郁症行为学评分及血清炎症介质[白细胞介素(IL)-1β、IL-6、肿瘤坏死因子-α(TNF-α)、IL-18]、海马组织中Toll样受体4(TLR4)、核因子κB(NF-κB)、NOD样受体热蛋白结构域相关蛋白3(NLRP3)、半胱氨酸蛋白酶(Caspase)-1水平。结果 与对照组比较，模型组、小剂量组、中剂量组、高剂量组和Flu组糖水偏好率下降，强迫游泳不动时间、悬尾不动时间均延长，矿场总路线缩短，血清IL-1β、IL-6、TNF-α、IL-18水平均升高，海马组织中TLR4、NF-κB、NLRP3、Caspase-1水平均升高，差异均有统计学意义(P<0.05);与模型组比较，小剂量组、中剂量组和高剂量组糖水偏好率升高，矿场总路线延长，强迫游泳不动时间、悬尾不动时间均缩短，血清IL-1β、IL-6、TNF-α、IL-18水平及海马组织中TLR4、NF-κB、NLRP3、Caspase-1水平均下降，且小剂量组、中剂量组、高剂量组小鼠抑郁症行为学评分、血清IL-1β、IL-6、TNF-α、IL-18水平及海马组织中TLR4、NF-κB、NLRP3、Capase-1水平均呈现明显剂量依赖性，差异均有统计学意义(P<0.05)。结论 ZSSP具有良好的抗抑郁作用，尤其是高剂量ZSSP抗抑郁效果更明显，其作用机制可能与抑制TLR4/NF-κB/NLRP3信号通路激活有关。更多还原

【Abstract】 Objective To investigate the effects of jujube seed polysaccharide(ZSSP) on depressive behavior in mice with chronic unpredictable mild stress(CUMS) and its mechanism.Methods Sixty SPF Kunming male mice were randomly divided into control group, model group, low-dose group, medium-dose group, high-dose group and fluoxetine hydrochloride(Flu) group.Except for the control group, the other five groups were treated with CUMS method to prepare depression models.The low-dose group, middle-dose group and high-dose groups were treated with 50,100,and 150 mg/kg ZSSP by gavage respectively.The depression behavior score, serum inflammatory mediators [interleukin(IL)-1β,IL-6,tumor necrosis factor-α(TNF-α),IL-18],Toll-like receptor 4(TLR4),nuclear factor-κB(NF-κB),NOD-like receptor pyrin domain-containing protein 3(NLRP3) and cysteinyl proteinase(Caspase)-1 level in hippocampus of each group were compared.Results Compared with the control group, the sucrose preference rate of the model group, the small-dose group, the medium-dose group, the high-dose group and the Flu group decreased, the forced swimming immobility time and tail suspension immobility time were prolonged, the total route of mine length was shortened, and the serum levels of IL-1β,IL-6,TNF-α and IL-18 were increased, and the levels of TLR4,NF-κB,NLRP3 and Caspase-1 in hippocampus were increased, and the differences were statistically significant(P<0.05).Compared with the model group, the sugar water preference rate increased in the low-dose group, medium-dose group and high-dose group, the total route of the mine manager was prolonged, the forced swimming immobility time and tail suspension immobility time were shortened, and the levels of serum IL-1β,IL-6,TNF-α,IL-18 and the levels of TLR4,NF-κB,NLRP3 and Caspase-1 in the hippocampal tissue decreased, and the depression behavior score, serum levels of IL-1β,IL-6,TNF-α,IL-18,and the levels of TLR4,NF-κB,NLRP3 and Capase-1 in the hippocampus of the low-dose group, medium-dose group and high-dose group showed significant dose-dependent differences(P<0.05).Conclusion ZSSP has a good antidepressant effect, especially the high dose of ZSSP,which mechanism of action may be related to the inhibition of TLR4/NF-κB/NLRP3 signaling pathway activation.更多还原